Combining targeted panel-based resequencing and copy-number variation analysis for the diagnosis of inherited syndromic retinopathies and associated ciliopathies
Author
Sánchez-Navarro, Iker; Da Silva, Luciana R.J.; Blanco-Kelly, Fiona; Zurita, Olga; Sánchez-Bolivar, Noelia; Villaverde, Cristina; López-Molina, María Isabel; García-Sandoval, Blanca; Tahsin-Swafiri, Saoud; Minguez, Pablo; Riveiro Álvarez, Rosa; Lorda, Isabel; Sánchez-Alcudia, Rocío; Pérez-Carro, Raquel; Valverde, Diana; Liu, Yichuan; Tian, Lifeng; Hakonarson, Hakon; Ávila-Fernández, Almudena; Corton, Marta; Ayuso, CarmenEntity
UAM. Departamento de Cirugía; Instituto de Investigación Sanitaria Fundación Jiménez Díaz (IIS-FJD)Publisher
Nature Publishing GroupDate
2018-12-01Citation
10.1038/s41598-018-23520-1
Scientific Reports 8 (2018): 5285
ISSN
2045-2322DOI
10.1038/s41598-018-23520-1Funded by
This study was funded by several grants from the Instituto de Salud Carlos III (ISCIII) from the Spanish Ministry of Health, including CIBERER (06/07/0036), FIS - FEDER (European Regional Development Fund) (PI016/00425), IIS-FJD Biobank PT13/0010/0012. In addition, sponsored chair HU-FJD-UAM “Cátedra de Patrocinio Medicina Genómica”, the Spanish National Organization of the Blind (ONCE) and the Spanish Fighting Blindness Foundation (FUNDALUCE) also supported our work. ISN and RSA are sponsored by Sara Borrell Postdoctoral Program (CD13-00085 and CD12-00676) from ISCIII/FEDER. MC is supported by the Miguel Servet Program (CP12/03256) from ISCIII/FEDER. RPC is supported by Fundación Conchita Rábago and LRJS is supported by CAPES Foundation, Ministry of Education of BrazilProject
Gobierno de España. PI016/00425; Gobierno de España. PT13/0010/0012Editor's Version
https://doi.org/10.1038/s41598-018-23520-1Subjects
Retinopathies; Retinal ciliopathies; 18 genes; Ciliary CEP41 gene; Phenotypic and genotypic; MedicinaRights
© 2018 The Author(s)Abstract
Inherited syndromic retinopathies are a highly heterogeneous group of diseases that involve retinal anomalies and systemic manifestations. They include retinal ciliopathies, other well-defined clinical syndromes presenting with retinal alterations and cases of non-specific multisystemic diseases. The heterogeneity of these conditions makes molecular and clinical characterization of patients challenging in daily clinical practice. We explored the capacity of targeted resequencing and copy-number variation analysis to improve diagnosis of a heterogeneous cohort of 47 patients mainly comprising atypical cases that did not clearly fit a specific clinical diagnosis. Thirty-three likely pathogenic variants were identified in 18 genes (ABCC6, ALMS1, BBS1, BBS2, BBS12, CEP41, CEP290, IFT172, IFT27, MKKS, MYO7A, OTX2, PDZD7, PEX1, RPGRIP1, USH2A, VPS13B, and WDPCP). Molecular findings and additional clinical reassessments made it possible to accurately characterize 14 probands (30% of the total). Notably, clinical refinement of complex phenotypes was achieved in 4 cases, including 2 de novo OTX2-related syndromes, a novel phenotypic association for the ciliary CEP41 gene, and the co-existence of biallelic USH2A variants and a Koolen-de-Vries syndrome-related 17q21.31 microdeletion. We demonstrate that combining next-generation sequencing and CNV analysis is a comprehensive and useful approach to unravel the extensive phenotypic and genotypic complexity of inherited syndromic retinopathies
Files in this item
Google Scholar:Sánchez-Navarro, Iker
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Da Silva, Luciana R.J.
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Blanco-Kelly, Fiona
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Zurita, Olga
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Sánchez-Bolivar, Noelia
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Villaverde, Cristina
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López-Molina, María Isabel
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García-Sandoval, Blanca
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Tahsin-Swafiri, Saoud
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Minguez, Pablo
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Riveiro Álvarez, Rosa
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Lorda, Isabel
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Sánchez-Alcudia, Rocío
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Pérez-Carro, Raquel
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Valverde, Diana
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Liu, Yichuan
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Tian, Lifeng
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Hakonarson, Hakon
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Ávila-Fernández, Almudena
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Corton, Marta
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Ayuso, Carmen
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